T-Cell Development, Maturation, and Activation

In the thymus, 107 thymocytes are produced daily, but the vast majority of cells undergo apoptosis during positive and negative selections, and only 1–3% of thymocytes eventually develop and mature to become CD4+ or CD8+T cells. Those T cells that cannot bind to their own MHC during development are induced to apoptosis, a process called positive selection. Thus, thymocytes that survive positive selection are able to bind to their own MHC, which determines the MHC-restricted nature of T cells, i.e., T cells only recognize cells that express their own MHC. However, those thymocytes that bind too strongly to their own MHC or MHC + Ag are likewise induced to apoptosis, a process called negative selection, because cells that bind too strongly to their own MHC or MHC + Ag will be activated when they enter peripheral blood and tissues, attacking their own tissues and causing autoimmune diseases. T-cell development and maturation are central to immunology and are the focus of this chapter.